Analysis Showed Teriparatide Reduced Fracture Risk Independent of Bone Turnover

Analysis Showed Teriparatide Reduced Fracture Risk Independent of
Bone Turnover 


SEATTLE, Wash., Oct. 4  /PRNewswire-FirstCall/ -- Data presented today at the
26th annual meeting of the American Society for Bone and Mineral Research
(ASBMR) show that the ability of teriparatide to prevent fractures remained
consistent regardless of pretreatment bone turnover status.

Bone is living tissue that constantly regenerates itself by breaking down and
reforming, a process referred to as bone turnover.  Osteoporosis can occur when
bone break down exceeds bone formation.

"In most cases, rapid bone turnover can be dangerous and lead to fracture in
osteoporotic patients," said the study's primary investigator, Pierre Delmas,
MD, Claude Bernard University of Lyon, France.  "In this study, regardless of
whether patients had high turnover rates before being treated, we saw a reduced
risk of fractures with teriparatide."

This post-hoc analysis examined biochemical markers of bone turnover, which
provide information about the rate of bone turnover.  This rate can vary
considerably in postmenopausal women with osteoporosis.  In this study, the
impact of the pretreatment bone turnover rate on the response to teriparatide
was examined.

FORTEO(R) (teriparatide [rDNA origin] injection), the first and only bone
formation agent approved for the treatment of osteoporosis, was granted FDA
approval in November 2002.  It stimulates new bone formation by increasing the
number and activity of bone forming cells called osteoblasts.  FORTEO is
approved for the treatment of osteoporosis in postmenopausal women who are at
high risk for fracture and to increase bone mass in men with primary or
hypogonadal osteoporosis who are at high risk for fracture.  These include men
(and postmenopausal women) with a history of osteoporosis-related fracture, or
who have multiple risk factors for fracture, or who have failed or are
intolerant to previous osteoporosis therapy, based upon physician assessment.

Until FORTEO's approval, the only approved osteoporosis treatments were
antiresorptives, which work mainly to slow or stop bone loss by reducing the
number and action of bone-removing cells called osteoclasts.

About the Analysis

To determine whether rate of bone turnover affects teriparatide's effect, this
analysis looked at the relationship between baseline biochemical markers of
bone turnover and the ability of teriparatide to reduce the occurrence of
fractures.

Five biochemical markers from postmenopausal women with osteoporosis who
participated in the pivotal FORTEO Fracture Prevention Trial were analyzed.

The Fracture Prevention Trial (FPT), a registration trial for FORTEO, was a
randomized, double-blinded, placebo controlled study that enrolled 1,637 women
with osteoporosis.  Subjects were randomized to teriparatide 20 mcg/day
(marketed as FORTEO), teriparatide 40 mcg/day or placebo for a median of 19
months.

A subset of 520 women had biochemical markers of bone turnover (serum
bone-specific alkaline phosphatase [BSAP], serum carboxy-terminal extension
peptide of procollagen type 1 [PICP], urinary N-terminal telopeptide [NTX], and
urinary free deoxypyridinoline [DPD]) measured at baseline.  A partially
overlapping subset of 771 women also had serum amino-terminal extension of
peptide of procollagen type 1 [PINP] evaluated at baseline.  BSAP, PICP and
PINP are all markers of bone formation, whereas DPD and NTX are markers of bone
resorption.

Analysis found that subjects with higher baseline concentrations of BSAP, PINP,
NTX and DPD had a higher risk of a new fragility fracture.  Teriparatide
significantly reduced the risk of vertebral and nonvertebral fragility
fractures regardless of pretreatment bone turnover, according to study results.

Important Safety Information about FORTEO

In two-year studies in rats, teriparatide caused an increase in the incidence
of osteosarcoma, a malignant bone tumor, which was dependent on dose and
duration of treatment.  Although no case of osteosarcoma has been reported in
the patients who received FORTEO in clinical trials, it is not known if humans
treated with FORTEO are at increased risk for this cancer.

FORTEO should be prescribed only to patients for whom the potential benefits
are considered to outweigh the potential risk.  The drug should not be
prescribed for patients at increased baseline risk for osteosarcoma, including
patients with Paget's disease of bone or unexplained elevations of alkaline
phosphatase, children or growing adults, or those who have had prior external
beam or implant radiation therapy involving the skeleton. Additionally,
patients with bone metastases or a history of skeletal malignancies, and those
with metabolic bone diseases other than osteoporosis, should not receive
FORTEO.  Patients with high levels of calcium in their blood should not receive
FORTEO due to the possibility of increasing their blood levels of calcium.

In clinical trials, the most frequent treatment-related adverse events reported
at the 20-microgram (mcg) dose approved for marketing were mild, similar to
placebo and generally did not require discontinuation of therapy. Reported
adverse events that appeared to be increased by FORTEO treatment were leg
cramps and dizziness (2.6 and 8 percent, respectively), compared with placebo
(1.3 percent and 5.4 percent, respectively).

FORTEO is supplied in a disposable pen device that can be used for up to 28
days to give once-daily self-administered injections.  FORTEO is available in a
20-mcg dose and should be taken for a period of up to 24 months.  Lilly has
implemented a risk management program that includes comprehensive measures
regarding the appropriate use of FORTEO in the target patient population.  A
Medication Guide explaining the details of the drug to the patient also
accompanies the product.  FORTEO also has a black box warning in its package
insert about the osteosarcoma findings in rats during preclinical testing. For
full prescribing information, please visit http://www.forteo.com/ .

About Osteoporosis

More than 50 percent of all women over the age of 75 are estimated to have
osteoporosis, and due to their advanced age, have a high risk of fracture.  In
fact, most American women over the age of 50 will experience one or more
osteoporosis-related fractures during their lifetimes, and women with
osteoporosis who have two or more previous fractures have up to a nine times
greater risk of future fracture compared with women who have not suffered a
previous fracture.

About Lilly

Lilly, a leading innovation-driven corporation is developing a growing
portfolio of first-in-class and best-in-class pharmaceutical products by
applying the latest research from its own worldwide laboratories and from
collaborations with eminent scientific organizations.  Headquartered in
Indianapolis, Ind., Lilly provides answers -- through medicines and information
-- for some of the world's most urgent medical needs.  Additional information
about Lilly is available at http://www.lilly.com/ .

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DATASOURCE: Eli Lilly and Company



CONTACT: Keri S. McGrath of Eli Lilly and Company, Cell: [phone],

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